DESCRIPTION (Verbatim from Applicant's Abstract): H. ducreyi is the causative agent of chancroid, a disease characterized by genital ulcers, and in 50 percent of the cases, inguinal lymphadenopathy. The occurrence of chancroid outbreaks in the United States coupled with its association with the heterosexual transmission of HIV in Africa makes understanding the pathogenesis of this disease imperative so that rational intervention strategies can be devised. We have developed a primate model for chancroid that measures the effect of disease progression from the pustular to the ulceral to the resolution stages of disease at a genital site in an animal closely related to humans. We now intend to use the primate model to study the local and systemic immune response induced by infection with H. ducreyi and the immunobiology of chancroidal disease. We hypothesize that a predominant Th1 response will be induce and will correlated with clearance of the organism from genital tissues. We have previously shown that H. ducreyi produces a toxin, which has been termed a hemolysin, based on its ability to lyse red blood cells, although its role in pathogenesis undoubtedly depends upon its ability to affect other cells important in chancroidal lesions. We have shown that immunization with hemolysin increases the clearance of a homologous strain of H. ducreyi from lesions in the temperature-dependent rabbit model and now intend to study the nature of immune response that enhances clearance of this organism from genital tissues in the primate model. Thus, we propose to study the ability of immunization with hemolysin (compared to immunization with H. ducreyi cell envelopes) to attenuate lesion development and enhance clearance of H. ducreyi from genital ulcers. We also propose to study the effect of immunization on the systemic and local immune response, localization of H. ducreyi in primate lesions, cellular and antibody response to individual antigens, and the possible mechanism of protection by antibodies from immunized primates. We have previously shown that the target cell range of hemolysin includes keratinocytes, fibroblasts, lymphocytes, and macrophages and hypothesize that hemolysin enhances ulcer development, evasion of the immune response in chancroidal disease, and survival of H. ducreyi in genital lesions. Thus we will study the contribution of hemolysin to lesion progression and survival of H. ducreyi in primate genital ulcers and the effect of hemolysin expression on the local and systemic immune response. These studies will provide a better understanding of the role of the H. ducreyi hemolysin in the pathogenesis and immunobiology of chancroid and will provide a groundwork on which to base future strategies for vaccine development for chancroid.